10-79612325-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005411.5(SFTPA1):c.186A>G(p.Pro62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,446 control chromosomes in the GnomAD database, including 24,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2661 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21977 hom. )

Consequence

SFTPA1
NM_005411.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.93

Variant links:

Genes affected

SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

SFTPA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 10-79612325-A-G is Benign according to our data. Variant chr10-79612325-A-G is described in ClinVar as [Benign]. Clinvar id is 165197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFTPA1	NM_005411.5 linkuse as main transcript	c.186A>G	p.Pro62=	synonymous_variant	4/6	ENST00000398636.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFTPA1	ENST00000398636.8 linkuse as main transcript	c.186A>G	p.Pro62=	synonymous_variant	4/6	1	NM_005411.5	P1	Q8IWL2-1
SFTPA1	ENST00000419470.6 linkuse as main transcript	c.231A>G	p.Pro77=	synonymous_variant	4/6	1			Q8IWL2-2
SFTPA1	ENST00000428376.6 linkuse as main transcript	c.186A>G	p.Pro62=	synonymous_variant	3/5	1		P1	Q8IWL2-1
SFTPA1	ENST00000429958.5 linkuse as main transcript	c.186A>G	p.Pro62=	synonymous_variant	3/5	1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27012

AN:

151896

Hom.:

2651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.206

AC:

51721

AN:

251438

Hom.:

6067

AF XY:

0.203

AC XY:

27584

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.270

Gnomad SAS exome

AF:

0.251

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.167

AC:

244707

AN:

1461434

Hom.:

21977

Cov.:

AF XY:

0.169

AC XY:

123216

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.246

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.178

AC:

27062

AN:

152012

Hom.:

2661

Cov.:

AF XY:

0.183

AC XY:

13619

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.276

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.218

Alfa

AF:

0.143

Hom.:

740

Bravo

AF:

0.187

Asia WGS

AF:

0.289

AC:

1003

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 13, 2013

Benign based on MAF in ESP (16.7% in AA; 15.82% in EA) -

SFTPA1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

Cadd

Benign

0.43

Dann

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over